U.S. patent number 11,154,234 [Application Number 15/707,190] was granted by the patent office on 2021-10-26 for method for the management of nociception.
This patent grant is currently assigned to CYBERBRO TECHNOLOGIES. The grantee listed for this patent is CYREBRO TECHNOLOGIES. Invention is credited to Quentin Barthelemy, Louis Mayaud.
United States Patent |
11,154,234 |
Barthelemy , et al. |
October 26, 2021 |
Method for the management of nociception
Abstract
The present invention relates to a computer-implemented method
for modifying nociception in a subject using
electroencephalographic data acquired from the brain of a subject,
the method comprising the steps of: receiving
electroencephalographic data comprising at least two
electroencephalographic signals measured simultaneously from at
least two electroencephalogram channels, computing a Fourier
transform of the at least two electroencephalographic signals on a
temporal window; averaging complex Fourier coefficients in the
frequency band of alpha waves; computing an alpha phase
concentration neuromarker on consecutive epochs of the
electroencephalographic data, generating a sensorial stimulus
representing alpha phase concentration neuromarker using an output
generator. The present invention also relates to a method for
training a subject to reinforce self-modulation of pain
pathways.
Inventors: |
Barthelemy; Quentin (Lyons,
FR), Mayaud; Louis (Angouleme, FR) |
Applicant: |
Name |
City |
State |
Country |
Type |
CYREBRO TECHNOLOGIES |
Paris |
N/A |
FR |
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Assignee: |
CYBERBRO TECHNOLOGIES (Paris,
FR)
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Family
ID: |
1000005889804 |
Appl.
No.: |
15/707,190 |
Filed: |
September 18, 2017 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20190082991 A1 |
Mar 21, 2019 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B
5/7405 (20130101); A61B 5/7257 (20130101); A61B
5/743 (20130101); A61B 5/7203 (20130101); G16H
20/40 (20180101); A61B 5/374 (20210101); G16H
50/20 (20180101); A61B 5/377 (20210101); A61B
5/316 (20210101); G16H 20/10 (20180101); A61B
5/375 (20210101); A61B 2505/09 (20130101) |
Current International
Class: |
A61B
5/00 (20060101); A61B 5/316 (20210101); G16H
20/40 (20180101); G16H 20/10 (20180101); G16H
50/20 (20180101); A61B 5/375 (20210101); A61B
5/374 (20210101); A61B 5/377 (20210101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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3181043 |
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Jun 2017 |
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EP |
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2008124566 |
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Oct 2008 |
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WO |
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Other References
Mormann, F. et al., "Mean phase coherence as a measure for phase
synchronization and its application to the EEG of epilepsy
patients," Physica D: Nonlinear Phenomena, 2000, 144.3-4: 358-369.
cited by applicant .
International Search Report dated Feb. 8, 2019 in corresponding
International Application No. PCT/EP2018/075208. cited by applicant
.
Jorn M. Horshig, et al., Directed Communication between Nucleus
Accumbens and Neocortex in Humans Is Differentially Supported by
Synchronization in the Theta and Alpha Band, PLoS ONE, Sep. 22,
2015, pp. 1-20, vol. 10, No. 9. cited by applicant .
Wenjie Ren, et al., The indirect pathway of the nucleus accumbens
shell amplifies neuropathic pain, Nature Neuroscience, 2016, pp.
1-13. cited by applicant .
Eduardo E. Benarroch, Involvement of the nucleus accumbens and
dopamine system in chronic pain, Neurology, 2016, pp. 1-7. cited by
applicant .
Marwan N. Baliki, et al., Predicting Value of Pain and Analgesia:
Nucleus Accumbens Response to Noxious Stimuli Changes in the
Presence of Chronic Pain, Neuron, Apr. 15, 2010, pp. 149-160, vol.
66, Elsevier Inc. cited by applicant .
Pei-Ching Chang, et al., Role of Nucleus Accumbens in Neuropathic
Pain: Linked Multi-Scale Evidence in the Rat Transitioning to
Neuropathic Pain, Pain, 2015, pp. 1-26. cited by applicant .
Neil Schwartz, et al., Decreased motivation during chronic pain
requires long-term depression in the nucleus accumbens, Science,
2015, pp. 1-16. cited by applicant .
Marco Congedo, et al., On the Blind Source Separation of Human
Electroencephalogram by Approximate Joint Diagonalization of Second
Order Statistics, Clinical Neurophysiology, 2008, pp. 1-37, vol.
119. cited by applicant .
A.S. Zigmond, et al., The Hospital Anxiety and Depression Scale,
Acta Psychiatrica Scandinavica, 1983, pp. 361-370, vol. 67. cited
by applicant .
G. Frank Lawlis, et al., The Development of the Dallas Pain
Questionnaire: An Assessment of the Impact of Spinal Pain on
Behavior, Spine, 1989, pp. 511-516. vol. 14, No. 5. cited by
applicant .
Max Hamilton, The Assessment of Anxiety States by Rating, 1959, pp.
50-55. cited by applicant.
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Primary Examiner: Chen; Tse W
Assistant Examiner: Catina; Michael A
Attorney, Agent or Firm: Nixon & Vanderhye
Claims
The invention claimed is:
1. A computer-implemented method for modifying nociception in a
subject using electroencephalographic data acquired from a brain of
the subject, the method comprising: a) receiving
electroencephalographic data comprising at least two
electroencephalographic signals measured simultaneously from at
least two electroencephalogram channels; b) computing a Fourier
transform of the at least two electroencephalographic signals on a
temporal window; c) averaging complex Fourier coefficients in the
frequency band of alpha waves; d) computing an alpha phase
concentration neuromarker (APC) on consecutive epochs of the
electroencephalographic data according to the formula
.times..times..times..times..times..phi. ##EQU00005## wherein N is
total number of channels in the received electroencephalographic
data and .phi..sub.n is a phase in the alpha band in the channel n;
and e) generating a sensorial stimulus representing the alpha phase
concentration neuromarker and stimulating the subject by providing
said sensorial stimulus to the subject using an output generator so
as to modify the nociception of the subject, wherein the sensorial
stimulus is one selected from the group consisting of: visual
stimulus, and auditory stimulus.
2. The computer-implemented method according to claim 1, wherein
the computing of the Fourier transform of the at least two
electroencephalographic signals is preceded by removing noise
and/or artefact from the electroencephalographic signals.
3. The computer-implemented method according to claim 1, wherein
the sensorial stimulus representing alpha phase concentration
neuromarker is communicated to the subject.
4. The computer-implemented method according to claim 1, wherein
the sensorial stimulus is communicated to the subject in real
time.
5. The computer-implemented method according to claim 1, wherein
said method is controlled by the subject.
6. The computer-implemented method according to claim 1, wherein
said method is supervised by a skilled physician.
7. The computer-implemented method according to claim 1, wherein
the method is a long-term treatment for the subject.
8. A system for modifying nociception in a subject, the system
comprising: an acquisition set-up for acquiring at least two
electroencephalographic signals from the subject; a data processing
system comprising means for carrying out the steps of: a) receiving
electroencephalographic data comprising at least two
electroencephalographic signals measured simultaneously from at
least two electroencephalogram channels, b) computing a Fourier
transform of the at least two electroencephalographic signals on a
temporal window, c) averaging complex Fourier coefficients in the
frequency band of alpha waves, d) computing an alpha phase
concentration neuromarker (APC) on consecutive epochs of the
electroencephalographic data according to the formula
.times..times..times..times..times..phi. ##EQU00006## wherein N is
total number of channels in the received electroencephalographic
data and .phi..sub.n is a phase in the alpha band in the channel n,
and e) generating a sensorial stimulus representing the alpha phase
concentration neuromarker; and an output generator, by which the
data processing system generates the sensorial stimulus, which is
configured to stimulate the subject by providing to the subject the
sensorial stimulus representing the alpha phase concentration
neuromarker so as to modify the nociception of the subject, wherein
the sensorial stimulus is one selected from the group consisting
of: visual stimulus, and auditory stimulus.
9. A non-transitory, computer-readable storage medium comprising
instructions which, when executed by a computer, cause the computer
to carry out a computer-implemented method for modifying the
nociception in a subject using electroencephalographic data
acquired from a brain of the subject, said method comprising: a)
receiving electroencephalographic data comprising at least two
electroencephalographic signals measured simultaneously from at
least two electroencephalogram channels; b) computing a Fourier
transform of the at least two electroencephalographic signals on a
temporal window; c) averaging complex Fourier coefficients in the
frequency band of alpha waves; d) computing an alpha phase
concentration neuromarker (APC) on consecutive epochs of the
electroencephalographic data according to the formula
.times..times..times..times..times..phi. ##EQU00007## wherein N is
total number of channels in the received electroencephalographic
data and .phi..sub.n is a phase in the alpha band in the channel n;
and e) generating a sensorial stimulus representing alpha phase
concentration neuromarker and stimulating the subject by providing
said sensorial stimulus to the subject using an output generator so
as to modify the nociception of the subject, wherein the sensorial
stimulus is one selected from the group consisting of: visual
stimulus, and auditory stimulus.
Description
FIELD OF INVENTION
The present invention pertains to the field of self-paced brain
neuromodulation and more particularly, but not exclusively to
methods and systems for analyzing and representing
neurophysiological data in order to cause a modification of the
perception of pain in a subject.
BACKGROUND OF INVENTION
Self-paced brain neuromodulation is a training procedure that
teaches self-control of brain function to a subject by measuring
brain waves and providing real-time stimuli in response. During
this procedure, the subject becomes aware of the changes occurring
during training and will be able to assess his progress in order to
achieve optimum performances. More specifically, the
perceptualization of a specific brain activity allows the subject
to learn to increase or decrease the said brain activity thanks to
experimental psychology paradigms such as operant condition or
self-regulation. There is now a long-standing evidence that a
subject undergoing several neuromodulation training sessions is
able to modify plasticity and generate anatomical and functional
changes in the subject brain. Those modifications have also
long-been associated with clinical improvement in various central
nervous system conditions and chronic pain. Self-paced brain
neuromodulation represents a great deal of interest especially for
patients non-responding to classical clinical treatment such as
medicaments, surgery or physical therapy and facing a therapeutic
dead-end. The self-paced brain neuromodulation method, disclosed in
the present invention, modifies a subject pain perception, also
known as nociception.
The use of self-paced brain neuromodulation for the modification of
subject nociception has already been suggest by John et al. (WO
2008/124566).
John et al. discloses a method for presenting a pain quantification
index and a target index to perform a self-paced brain
neuromodulation allowing the subject to reduce the sensation and
intensity of pain. Said pain quantification index is estimated by
comparison to a reference brain wave data obtained from a
population normative data indicative of various reference brain
wave activity (i.e. brain wave activity representative of pain
absence in a subject). However, the calculation of brain activity
reference is a time-consuming procedure and does not represent a
reliable reference for all subject since it does not take in
consideration the large variability of pathologies and therefore
performances between subjects. Precisely, a subject experiencing
pain is likely to exhibit changes in multiple brain areas so that
the intervention is inherently non-specific.
In this context, rises the necessity to develop an easier to
implement and more reliable method which uses a patient-specific
reference.
The present invention discloses an improved self-paced brain
neuromodulation. In the present invention, the neural activity of a
subject is evaluated through the calculation of a brain activity
neuromarker and the variation of said neuromarker respect to a
reference state is reported in real time to the subject in order to
enable said subject to modulate its neural activity towards
improved nociception state by self-paced neuromodulation.
SUMMARY
A first aspect of the present invention relates to a method for
modifying nociception in a subject using electroencephalographic
data acquired from the brain of a subject, the method comprising
the following steps: a) receiving electroencephalographic data
comprising at least two electroencephalographic signals measured
simultaneously from at least two electroencephalogram channels; b)
computing a Fourier transform of the at least two
electroencephalographic signals on a temporal window; c) averaging
complex Fourier coefficients in the frequency band of alpha waves;
d) computing an alpha phase concentration neuromarker (APC) on
consecutive epochs of the electroencephalographic data according to
the formula
.times..times..times..times..times..phi. ##EQU00001## wherein N is
total number of channels in the received electroencephalographic
data and .phi..sub.n is a phase in the alpha band in the channel n;
and e) generating a sensorial stimulus representing alpha phase
concentration neuromarker using an output generator.
According to one embodiment, the method for modifying nociception
is a computer-implemented method.
Another aspect of the present invention relates to a method for
generating a first sensorial stimulus using electroencephalographic
data acquired from the brain of a subject, the method comprising
the following steps: a) receiving electroencephalographic data
comprising at least two electroencephalographic signals measured
simultaneously from at least two electroencephalogram channels; b)
computing a Fourier transform of the at least two
electroencephalographic signals on a temporal window; c) averaging
complex Fourier coefficients in the frequency band of alpha waves;
d) computing an alpha phase concentration neuromarker (APC) on
consecutive epochs of the electroencephalographic data according to
the formula
.times..times..times..times..times..phi. ##EQU00002## wherein N is
total number of channels in the received electroencephalographic
data and .phi..sub.n is a phase in the alpha band in the channel n;
and e) generating a first sensorial stimulus representing alpha
phase concentration neuromarker using an output generator.
All the embodiments relating to the method for modifying
nociception may be applied to the method for generating a first
sensorial stimulus. Therefore, in the following description only
the method for modifying nociception will be described in details.
The "first sensorial stimulus" may be understood more generally as
"sensorial stimulus" as described in the following description.
According to one embodiment, the step b) of the method according to
the first aspect of the present invention is preceded by the step
of removing the noise and/or artefact from the
electroencephalographic signals.
According to one embodiment, the sensorial stimulus representing
alpha phase concentration neuromarker is communicated to the
subject.
According to one embodiment, the sensorial stimulus is communicated
to the subject in real time.
According to one embodiment, the sensorial stimulus representation
the numerical value of the alpha phase concentration neuromarker is
a visual stimulus.
the sensorial stimulus representation the numerical value of the
alpha phase concentration neuromarker is an auditive stimulus.
According to one embodiment, the method according to the first
aspect of the present invention is controlled by a subject.
According to one embodiment, the method according to the first
aspect of the present invention is supervised by a skilled
physician.
According to one embodiment, the subject suffers from a chronic
pain.
According to one embodiment, the subject is a cancer survivor
suffering from chemotherapy-induced peripheral neuropathy.
According to one embodiment, the method according to the first
aspect of the present invention is a long-term cure for the
subject.
The present invention further relates to a system for modifying
nociception in a subject, the system comprising: acquisition set-up
for acquiring at least two electroencephalographic signals from a
subject; a data processing system comprising means for carrying out
the steps of the method according to the first aspect of the
present invention; and output generator for reporting the sensorial
stimulus representation the numerical value of the alpha phase
concentration neuromarker.
The present invention further relates to a computer program product
for modifying nociception in a subject, the computer program
product comprising instructions which, when the program is executed
by a computer, cause the computer to carry out the steps of the
method described hereabove.
The present invention further relates to a computer-readable
storage medium comprising instructions which, when the program is
executed by a computer, cause the computer to carry out the steps
of the method described hereabove.
A second aspect of the present invention relates to a method for
training a subject to reinforce self-modulation of pain pathways
using electroencephalographic data acquired from the brain of a
subject, the method comprising the following steps: a) receiving
the electroencephalographic data comprising at least two
electroencephalographic signals measured simultaneously from at
least two electroencephalogram channels; b) filtering the at least
two electroencephalographic signals in at least one frequency band
with at least one band-pass filter, wherein one of the at least one
band-pass filter filters the at least two electroencephalographic
signals in the frequency band of alpha waves; c) computing an
average over the electroencephalographic channels obtaining an
averaged signal of the at least two electroencephalographic
signals; d) computing an alpha phase synchrony neuromarker as a
Frobenius squared norm a of the averaged signal on a temporal
window; and e) generating a sensorial stimulus representing alpha
phase synchrony neuromarker using an output generator.
According to one embodiment, the method for training a subject to
reinforce self-modulation of pain pathways is a
computer-implemented method.
Yet another aspect of the present invention relates to a method for
generating a second sensorial stimulus using
electroencephalographic data acquired from the brain of a subject,
the method comprising the following steps: a) receiving the
electroencephalographic data comprising at least two
electroencephalographic signals measured simultaneously from at
least two electroencephalogram channels; b) filtering the at least
two electroencephalographic signals in at least one frequency band
with at least one band-pass filter, wherein one of the at least one
band-pass filter filters the at least two electroencephalographic
signals in the frequency band of alpha waves; c) computing an
average over the electroencephalographic channels obtaining an
averaged signal of the at least two electroencephalographic
signals; d) computing an alpha phase synchrony neuromarker as a
Frobenius squared norm a of the averaged signal on a temporal
window; and e) generating a second sensorial stimulus representing
alpha phase synchrony neuromarker using an output generator.
All the embodiments relating to the method for training a subject
to reinforce self-modulation of pain pathways may be applied to the
method for generating a second sensorial stimulus. Therefore, in
the following description only the method for training a subject to
reinforce self-modulation of pain pathways will be described in
details. The "second sensorial stimulus" may be understood more
generally as "sensorial stimulus" as described in the following
description.
According to one embodiment, the step d) of the method according to
the second aspect of the present invention is followed by a
normalization step comprising: a) computing a parameter p as the
global filed power of the averaged signal on a temporal window,
wherein said temporal window corresponds to the temporal window on
which is calculated the alpha phase synchrony neuromarker; and b)
normalizing the alpha phase synchrony neuromarker a by the global
field power of the averaged signal p.
According to one embodiment, the step c) of the method according to
the second aspect of the present invention is preceded by the step
of removing the noise and artefact from the electroencephalographic
signal.
According to one embodiment, the sensorial stimulus representing
alpha phase synchrony neuromarker is communicated to the
subject.
According to one embodiment, the sensorial stimulus is communicated
to the subject in real time.
According to one embodiment, the sensorial stimulus is a visual
representation of the alpha phase synchrony neuromarker numerical
value.
According to one embodiment, the subject is affected by a chronic
pain or a cognitive-related disorder.
The present invention further relates to a system for training a
subject to reinforce self-modulation of pain pathways, the system
comprising: acquisition set-up for acquiring at least two
electroencephalographic signals from a subject; a data processing
system comprising means for carrying out the steps of the method
according to the second aspect of the present invention; and output
generator for reporting the sensorial stimulus representation the
numerical value of the alpha phase synchrony neuromarker.
The present invention further relates to a computer program product
for training a subject to reinforce self-modulation of pain
pathways, the computer program product comprising instructions
which, when the program is executed by a computer, cause the
computer to carry out the steps of the method according to the
second aspect of the present invention.
The present invention further relates to a computer-readable
storage medium comprising instructions which, when the program is
executed by a computer, cause the computer to carry out the steps
of the method according to the second aspect of the present
invention.
Definitions
In the present invention, the following terms have the following
meanings: As used herein the singular forms "a", "an", and "the"
include plural reference unless the context clearly dictates
otherwise. The term "about" is used herein to mean approximately,
roughly, around, or in the region of. When the term "about" is used
in conjunction with a numerical range, it modifies that range by
extending the boundaries above and below the numerical values set
forth. In general, the term "about" is used herein to modify a
numerical value above and below the stated value by a variance of
20 percent, preferably of 5 percent. "Computing device" refers to a
computer-based system or a processor-containing system or other
system that can fetch and execute the instructions of a computer
program. "Electrode" refers to a conductor used to establish
electrical contact with a nonmetallic part of a circuit, preferably
a subject body. For instance, EEG electrodes are small metal discs
usually made of stainless steel, tin, gold, silver covered with a
silver chloride coating; there are placed on the scalp at specific
positions. "Electroencephalogram" or "EEG" refers to the tracing of
brain waves, by recording the electrical activity of the brain from
the scalp, made by an electroencephalograph.
"Electroencephalograph" refers to an apparatus for amplifying and
recording brain waves. "Epoch" refers to a determined period or
slice of neural signals. "Global field power" refers to the spatial
standard deviation, and it quantifies the amount of activity at
each time point in the field considering the data from all
recording electrodes simultaneously resulting in a
reference-independent descriptor of the potential field. "Real
time" refers to a process for which the output is given within a
time delay that is considered as smaller than the time delay
required to perform the underlying task of modulation adequately.
Therefore, for self-paced modulation, real time refers to a process
implemented in less than 700 ms, preferably less than 500 ms, more
preferably less than 400 ms, even more preferably less than 250 ms.
"Operand conditioning": refers a type of learning in which a
behavior is modified by the behavior's consequences, such as reward
or punishment. "Self-paced modulation" refers to the modulation of
the brain activity induced by the subject. In the sense of the
present invention, self-paced modulation has the same meaning as
neurofeedback and refers to the ability for the subject to control
its brain electrical activity by manipulating in real-time the
neuromarker. Self-paced modulation may or may not include cognitive
strategy such as predefined instructions given to the subject.
"State" refers to a mental status of the subject at a particular
time. "Subject" refers to a mammal, preferably a human. In the
sense of the present invention, a subject may be a patient, i.e. a
person receiving medical attention, undergoing or having underwent
a medical treatment, or monitored for the development of a
disease.
DETAILED DESCRIPTION
The present invention, in some embodiments thereof, relates to
neurophysiology and, more particularly, but not exclusively, to
computer-implemented method and system for analyzing
neurophysiological data for the purpose of modifying perception of
pain, such as, but not limited to, chronic pain.
Before describing at least one embodiment of the invention in
detail, it is to be understood that the invention is not
necessarily limited in its application to the details of
construction and the arrangement of the components and/or methods
set forth in the following description and/or illustrated in the
drawings and/or the examples. The invention is capable of other
embodiments or of being practiced or carried out in various
ways.
It is to be understood, unless otherwise defined, that
electroencephalographic signals and neural signals are both used to
define signals relating to the electrical activity of neurons
registered by electroencephalogram devices.
Accordingly, one or more aspects of the present disclosure relate
to computer-implemented methods implementing a self-paced brain
neuromodulation for modifying gating of painful stimuli. In FIG. 1,
a block diagram shows the main steps included in the
computer-implemented methods implemented in the present invention
embodiments. The computer implemented methods of the present
invention processes electroencephalographic signals and calculate
neuromarker associated to the brain waves in the alpha band. Alpha
waves are considered as "resting/idle state" neural oscillations in
the frequency range of 7.5-12.5 Hz arising from synchronous and
coherent (in phase or constructive) electrical activity of
populations of neurons such as the thalamic pacemaker cells in
humans. Furthermore, the synchrony of alpha waves was shown to be
involved in the corticostriatal communication in a way that suggest
that alpha synchrony actually modulates the nucleus accumbens (NAc)
activity ("Directed Communication between Nucleus Accumbens and
Neocortex in Humans Is Differentially Supported by Synchronization
in the Theta and Alpha Band", PloS one, Horschig et al., 2015). The
nucleus accumbens is a dopaminaregic area of the mesolimbic pathway
that participates in the central representation of pain but also
gates activity in ascending nociceptive pathways ("The indirect
pathway of the nucleus accumbens shell amplifies neuropathic pain",
Nature neuroscience, Ren et al., 2016).
More importantly, there is also a growing body of evidence
("Involvement of the nucleus accumbens and dopamine system in
chronic pain." Neurology, Benarroch, 2016) suggesting that the
chronification of pain rewires the nucleus accumbens in way that
also affects motivations and learning/reward circuitry involving
dopaminergic. In the very context of chronic pain, it has long been
reported experimentally that patients' nucleus accumbens activation
during noxious stimulation was very different to that of a
non-chronic population ("Predicting value of pain and analgesia:
nucleus accumbens response to noxious stimuli changes in the
presence of chronic pain." Neuron, Baliki et al., 2010). More
recent work on animal model even suggests that the changes
affecting the nucleus accumbens in presence chronic pain are both
macroscopic and molecular ("Role of nucleus accumbens in
neuropathic pain: linked multi-scale evidence in the rat
transitioning to neuropathic pain.", PAIN, Chang et al., 2014). The
impact of chronic pain on the nucleus accumbens also has indirect
consequence of more remote areas of the brain. For instance, the
drop in motivation elicited in mice by two different models of
chronic pain was proved to require a galanin receptor 1--triggered
depression of excitatory synaptic transmission in indirect pathway
nucleus accumbens medium spiny neurons ("Decreased motivation
during chronic pain requires long-term depression in the nucleus
accumbens." Science, Schwartz et al., 2014). These studies not only
show the importance of the nucleus accumbens in the perception and
affective processing of pain but also stress the importance of
lasting changes induces by chronic pain in this area as well as
networks of the prefrontal cortex affecting mental health
status.
According to one embodiment, the present invention comprises a
preliminary step 101 of receiving the electroencephalographic
signals acquired using electroencephalography from at least two
electrodes, positioned onto predetermined areas of the scalp of the
subject in order to obtain a multi-channel electroencephalographic
signals. According to one embodiment, the electroencephalographic
signals are acquired by at least 4, 8, 10, 15, 16, 17, 18, 19, 20,
21, 32, 64, 128 or 256 electrodes. According to one embodiment, the
electrodes are placed on the scalp according to the 10-10 or 10-20
system, dense-array positioning or any other electrodes positioning
known by the man skilled in the art. The electrodes montage may be
unipolar or bipolar. In a preferred embodiment, the electrodes are
placed accordingly to the 10-20 system with locations Fp1, Fp2, F7,
F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, O2, A1
and A2. In said embodiment, various types of suitable headsets or
electrode systems are available for acquiring such neural signals.
Examples includes, but are not limited to: Epoc headset
commercially available from Emotiv, Waveguard headset commercially
available from ANT Neuro, Versus headset commercially available
from SenseLabs, DSI 6 headset commercially available from Wearable
sensing, Xpress system commercially available from BrainProducts,
Mobita system commercially available from TMSi, Porti32 system
commercially available from TMSi, ActiChamp system commercially
available from BrainProducts and Geodesic system commercially
available from EGI. In an alternative embodiment, the
electroencephalographic signals are acquired using implanted
microelectrodes arrays or deep brain implants. According to one
embodiment, the electrical signals arising from neural activity are
acquired directly or indirectly using any cerebral imaging
technique known by one skilled in the art.
The electroencephalographic signals received may be obtained with a
standard recording module with sampling frequency of at least 24
Hz, preferably 32 Hz, 64 Hz, 128 Hz, 250 Hz or any other sampling
frequency known by the man skilled in the art.
According to one embodiment, the electroencephalographic signals
are received in real time.
According to one embodiment, the present invention further
comprises a step of pre-processing of the electroencephalographic
signals 102 in order to remove or reject noise. According to one
embodiment, the electroencephalographic signals are further
pre-processed in order to remove or reject artefact.
According to one embodiment, the electroencephalographic signals
from individual scalp electrodes is digitally filtered with at
least one filter chosen from group: low-frequency reject filter,
high-frequency reject filter, bandpass filter, band stop filter. In
a preferential embodiment, electroencephalographic signals may be
filtered using first-order Butterworth band-pass filter and a
third-order Butterworth notch filter; a skilled artisan would be
able to select a suitable range of frequencies to reject.
One or more of the following frequency bands may be extracted by
the filtering process: delta band (typically from about 1 Hz to
about 4 Hz), theta band (typically from about 3 to about 8 Hz),
alpha band (typically from about 7 to about 13 Hz), low beta band
(typically from about 12 to about 18 Hz), beta band (typically from
about 17 to about 23 Hz), and high beta band (typically from about
22 to about 30 Hz). Higher frequency bands, such as, but not
limited to, gamma band (typically from about 30 to about 80 Hz),
are also contemplated.
According to one embodiment, the artefacts are corrected from the
electroencephalographic signal using one or a combination of the
following techniques: adaptive filtering, Wiener filtering and
Bayes filtering, Hilbert-Huang Transform filter regression, blind
source separation (BSS), wavelet transform method, empirical mode
decomposition, nonlinear mode decomposition and the like.
One of the main source of physiological noise arises from eye
movements and more precisely from eye blinks which generates large
amplitude signals in the electroencephalographic signals. Those
ocular artefacts present a wide spectral distribution thus
perturbing all classic electroencephalographic bands, including the
alpha band which is the band of interest in the method disclosed by
the present invention.
In a one embodiment, the ocular artefacts are corrected using blind
source separation (BSS) or regression on an electrooculogram
trace.
According to one embodiment, the blind source separation for ocular
artefacts removal uses Fourier co-spectral matrices as descriptors
of the electroencephalographic signals, and these matrices are
jointly diagonalized, providing the mixing and the separating
matrices ("On the blind source separation of human
electroencephalogram by approximate joint diagonalization of second
order statistics", Clinical Neurophysiology, Congedo et al.,
2008).
The neuromarker derived from the alpha brain waves are calculated
103 on these filtered electroencephalographic signals.
According to one embodiment, a sensorial stimulus representing the
neuromarker derived from the alpha-band is generated by an output
generator, as show in FIG. 1, step 104. According to one
embodiment, said sensorial stimulus representing the alpha-derived
neuromarker is further communicated to the subject. According to
one embodiment, the acquisition and filtering processes according
to the embodiments described hereabove are computed in real time
and the sensorial stimuli are generated from the output generator
in real time and communicated to the subject in real time.
One or more forms of sensory stimulation may be used including, but
not limited to auditory, olfactory, tactile, somatosensory,
gustatory, vestibular, or other sensory systems stimuli. In a
preferred embodiment, the sensory stimulation is a visual
stimulation providing a visual representation of the numerical
value calculated for the alpha-derived neuromarker.
Typically, but not necessarily, the acquisition is a continuous
acquisition such that electroencephalographic data are collected
continuously before, during and after the generation of a
stimulus.
A first aspect of the present invention relates to a self-paced
neuromodulation method computer implemented for modifying
nociception in a subject using electroencephalographic data
acquired from the brain of a subject. In this first aspect, the
nociception modification is achieved by computing and communicating
to the subject an alpha-derived neuromarker value expressing the
phase coherence between alpha waves recorded from different
electrocardiographic channels: the alpha phase concentration
neuromarker.
According to one embodiment, the at least two
electroencephalographic signals, acquired and filtered as described
in the embodiment above, are decomposed into their frequencies
components by Fourier transform in a temporal window. Said temporal
window ranging from 0.5 s to 5 s, optionally the temporal window
may be of 0.5 seconds, 1 second, 1.5 seconds, 2 seconds, 2.5
seconds, 3 seconds, 3.5 seconds, 4 seconds, 4.5 seconds or 5
seconds. The signal transformation may be computed by numerical
integration of a series of ordered pairs, discrete Fourier
transform, or fast Fourier transform.
According to one embodiment, the Fourier transform is computed
after processing the signal with a window function of about 1 s
every x seconds, wherein x ranges from 0.05 s to 1 s. In a
preferred embodiment, the window function is an Hamming window.
According to one embodiment, the complex Fourier coefficients are
averaged in the band of alpha waves for each channel. These
averaged complex coefficients may be normalized in order to have
their absolute value equal to the unity.
According to one embodiment, the alpha phase concentration
neuromarker (APC) is computed on consecutive epochs of the
electroencephalographic data by averaging the normalized
coefficients over all channels according to the formula:
.times..times..times..times..times..phi. ##EQU00003## wherein N is
total number of channels in the received electroencephalographic
data and .phi..sub.n is a phase in the alpha band in the channel
n.
According to one embodiment, a sensorial stimulus representing the
value of the alpha phase concentration neuromarker is generated by
an output generator.
According to one embodiment, said sensorial stimulus representing
the value of the alpha phase concentration neuromarker is
communicated to the subject.
A second aspect of the present disclosure relates to a self-paced
neuromodulation method computer implemented for training a subject
in the self-modulation reinforcement of pain pathways using
electroencephalographic data acquired from the brain of a subject.
In this second aspect, the alpha-derived neuromarker calculated is
an alpha phase synchrony neuromarker dependent from the amplitude
and phase of the alpha waves.
According to one embodiment, the at least two
electroencephalographic signals, acquired as described in the
embodiments above, are filtered to remove noise and artefact
accordingly to the embodiment described above. According to one
embodiment, the at least two electroencephalographic signals are
filtered with a band-pass filter in at least one frequency band. In
said embodiment, one of the at least one band-pass filter filters
the at least two electroencephalographic signals in the frequency
band of alpha waves.
According to one embodiment, a spatial averaging operation is
computed over the electroencephalographic channels obtaining an
averaged signal of the at least two electroencephalographic
signals. According to one embodiment, on the spatially averaged
signal is applied a moving average window of about 2 s every
.DELTA.t, wherein .DELTA.t ranges from 0.05 s to 1 s.
According to one embodiment, the alpha phase synchrony neuromarker
(APS) is computed as a Frobenius squared norm a of the averaged
signal on a temporal window. Said temporal window ranging from 0.5
s to 5 s, optionally the temporal window may be of 0.5 seconds, 1
second, 1.5 seconds, 2 seconds, 2.5 seconds, 3 seconds, 3.5
seconds, 4 seconds, 4.5 seconds or 5 seconds.
According to one embodiment, the alpha phase synchrony neuromarker
is normalized by the global field power of the averaged signal p.
Said global field power is computed for the averaged signal on a
temporal window, wherein said temporal window corresponds to the
temporal window on which is calculated the alpha phase synchrony
neuromarker. The normalized alpha phase synchrony neuromarker
APS.sub.n may be obtained dividing the alpha phase synchrony
neuromarker a by the global field power signal p, as p or a
logarithmic normalization as follows
.function..function. ##EQU00004##
According to one embodiment, a sensorial stimulus representing the
alpha phase synchrony neuromarker is generated by an output
generator.
According to one embodiment, a sensorial stimulus representing the
alpha phase synchrony neuromarker is communicated to the
subject.
The electroencephalographic data can be analyzed immediately after
acquisition in a real time processing or it can be recorded and
stored and thereafter analyzed in a second time.
According to one embodiment, the self-paced neuromodulation methods
of the present invention are beneficial for any subject
experiencing pain. The subject may experience a transitory pain or
chronic pain, a nociceptive pain, a neuropathic pain, a psychogenic
pain, a breakthrough pain and/or a phantom pain.
In a specific embodiment, the self-paced neuromodulation methods of
the present invention are especially beneficial for subject
suffering from chronic pain such as chronic primary pain, chronic
cancer pain, chronic posttraumatic pain, chronic headache and
orofacial pain, chronic visceral pain or chronic musculoskeletal
pain.
In a specific embodiment, the self-paced neuromodulation methods of
the present invention are especially beneficial for subject
suffering from chronic musculoskeletal pain such as lower back
pain, myalgia, fibromyalgia, stress fractures, tunnel syndrome
including carpal tunnel syndrome, cubital tunnel syndrome and
tarsal tunnel syndrome, arthritic pain, muscle pain, repetitive
strain injury, inflammations, fibrosis or tissue degradation.
In a specific embodiment, the self-paced neuromodulation methods of
the present invention are especially beneficial for subject
suffering from chemotherapy-induced peripheral neuropathy.
The phrase "inflammatory pain" means pain due to edema or swelling
of any inflamed tissue, including inflammatory joint pain.
Inflammatory joint pain includes rheumatoid arthritic pain.
The phrase "acute pain" means any pain, including, but not limited
to, joint pain, osteoarthritic pain, rheumatoid arthritic pain,
inflammatory pain, pain from a burn, pain from a cut, surgical
pain, pain from fibromyalgia, bone cancer pain, menstrual pain,
back pain, headache, static allodynia, and dynamic allodynia, that
lasts from 1 minute to 91 days, 1 minute to 31 days, 1 minute to 7
days, 1 minute to 5 days, 1 minute to 3 days, 1 minute to 2 days, 1
hour to 91 days, 1 hour to 31 days, 1 hour to 7 days, 1 hour to 5
days, 1 hour to 3 days, 1 hour to 2 days, 1 hour to 24 hours, 1
hour to 12 hours, or 1 hour to 6 hours, per occurrence if left
untreated. Acute pain includes, but is not limited to, joint pain,
osteoarthritic pain, rheumatoid arthritic pain, inflammatory pain,
pain from a burn, pain from a cut, surgical pain, pain from
fibromyalgia, bone cancer pain, menstrual pain, back pain,
headache, static allodynia, dynamic allodynia, acute joint pain,
acute osteoarthritic pain, acute rheumatoid arthritic pain, acute
inflammatory pain, acute headache, acute menstrual pain, acute back
pain, and acute pain from fibromyalgia. Acute pain may be selected
from acute joint pain, acute osteoarthritic pain, acute rheumatoid
arthritic pain, acute inflammatory pain, acute headache, acute
menstrual pain, and acute back pain. Acute pain may be selected
from acute joint pain, acute osteoarthritic pain, acute rheumatoid
arthritic pain, and acute inflammatory pain. Acute pain may be
selected from acute joint pain, acute osteoarthritic pain, and
acute rheumatoid arthritic pain. Acute pain may be selected from
acute joint pain and acute osteoarthritic pain.
Further examples of disorder or conditions for which a subject
would benefit from the self-paced neuromodulation methods of the
present invention can be classified according to the present
embodiments include, without limitation, depression, attention
deficit hyperactivity disorder (ADHD), stroke, traumatic brain
injury (TBI), mild TBI (commonly known as brain concussion),
posttraumatic stress disorder (PTSD), epilepsy, Parkinson, multiple
sclerosis, agitation, Alzheimer's disease/dementia, anxiety, panic,
phobic disorder, bipolar disorder, borderline personality disorder,
behavior control problems, body dysmorphic disorder,
cognitive-related disorders (e.g., mild cognitive impairment),
dissociative disorders, eating disorder, appetite disorder,
fatigue, hiccups, impulse-control problems, irritability, mood
problems, movement problems, obsessive-compulsive disorder,
personality disorders, schizophrenia and other psychotic disorders,
seasonal affective disorder, sexual disorders, sleep disorders,
stuttering, substance abuse, Tourette's Syndrome, Trichotillomania,
or violent/self-destructive behaviors.
Nevertheless, the embodiments describing the self-paced
neuromodulation methods hereabove can be employed for any subject,
if desired.
The invention also relates to a system for modifying nociception in
a subject, the system comprising: acquisition set-up for acquiring
at least two electroencephalographic signals from a subject; a data
processing system comprising means for carrying out the steps of
the computer-implemented method according to anyone of the
embodiments described hereabove in relation with the first aspect
of the invention; and output generator for reporting the sensorial
stimulus representation the numerical value of the alpha phase
concentration neuromarker.
The present invention further relates to a system to reinforce
self-modulation of pain pathways in a subject, the system
comprising: acquisition set-up for acquiring at least two
electroencephalographic signals from a subject; a data processing
system comprising means for carrying out the steps of the
computer-implemented method according to anyone of the embodiments
described hereabove in relation with the second aspect of the
invention; and output generator for reporting the sensorial
stimulus representation the numerical value of the alpha phase
synchrony neuromarker.
Yet another aspect of the present invention relates to a system for
self-paced brain neuromodulation, the system comprising:
acquisition set-up for acquiring at least two
electroencephalographic signals from a subject; a data processing
system comprising means for carrying out the steps of the
computer-implemented method for modifying nociception in a subject
and the computer-implemented method to reinforce self-modulation of
pain pathways in a subject according to anyone of the embodiments
described hereabove; and output generator for reporting the
sensorial stimulus representation of the numerical value of the
alpha phase concentration neuromarker and/or alpha phase synchrony
neuromarker.
According to one embodiment, the acquisition set-up comprises any
means known by one skilled in the art enabling acquisition (i.e.
capture, record and/or transmission) of electroencephalographic
signals as defined in the present invention, preferably electrodes
or headset as explained hereabove. According to one embodiment, the
acquisition set-up comprises an amplifier unit for magnifying
and/or converting the electroencephalographic signals from analog
to digital format.
The present invention further relates to a computer program product
for modifying nociception in a subject, the computer program
product comprising instructions which, when the program is executed
by a computer, cause the computer to carry out the steps of the
computer-implemented method for modifying nociception according to
anyone of the embodiments described hereabove in relation with the
first aspect of the invention.
The present invention further relates to a computer program product
to reinforce self-modulation of pain pathways in a subject, the
computer program product comprising instructions which, when the
program is executed by a computer, cause the computer to carry out
the steps of the computer-implemented method to reinforce
self-modulation of pain pathways according to anyone of the
embodiments described hereabove in relation with the second aspect
of the invention.
According to one embodiment, the data processing system is a
dedicated circuitry or a general purpose computer, configured for
receiving the data and executing the operations described in the
embodiment described above. According to one embodiment, the data
processing system comprises a processor and a computer program. The
processor receives digitalized neural signals and processes the
digitalized electroencephalographic signals under the instructions
of the computer program to compute the neuromarker. According to
one embodiment, the computing device comprises a network connection
enabling remote implementation of the method according to the
present invention. According to one embodiment,
electroencephalographic signals are wirelessly communicated to the
data processing device. According to one embodiment, the output
generator wirelessly receives the alpha-derived neuromarker from
the data processing device.
The present invention further relates to a computer-readable
storage medium comprising instructions which, when the program is
executed by a computer, cause the computer to carry out the steps
of the computer-implemented method according to anyone of the
embodiments described hereabove.
Computer programs implementing the method of the present
embodiments can commonly be distributed to users on a distribution
computer-readable storage medium such as, but not limited to, an SD
card, an external storage device, a microchip, a flash memory
device and a portable hard drive. From the distribution medium, the
computer programs can be copied to a hard disk or a similar
intermediate storage medium. The computer programs can be run by
loading the computer instructions either from their distribution
medium or their intermediate storage medium into the execution
memory of the computer, configuring the computer to act in
accordance with the method of this invention. All these operations
are well-known to those skilled in the art of computer systems.
According to one embodiment, the output generator comprises any
means for reporting an alpha-derived neuromarker value. According
to one embodiment, the alpha-derived neuromarker value is reported
using visual means, auditory means, olfactory means, tactile means
(e.g. vibratory or haptic feedback) and/or gustatory means.
Preferably, the alpha-derived neuromarker value is reported using a
display such as lights; LEDs; a screen; a smartphone, a computer
monitor or a television; or a head-mounted display.
According to one embodiment, the self-paced neuromodulation methods
of the present invention are used to train self-paced
neuromodulation of a subject during multiple training session. The
number of training sessions may be of 5, 10, 15, 20, 25, 30, 35,
40, 45 or 50, preferably about 20. According to one embodiment,
each training session consists of multiple blocks, preferably 6
blocks, each of about a few minutes, notably 5 minutes. According
to one embodiment, the training sessions are made by the subject
during a period of time ranging from about a few days to about a
few weeks.
The reporting of the alpha-derived neuromarker value enables the
perceptualization of a specific brain activity, such as
nociception, allowing the subject to learn to increase or decrease
said specific brain activity. According to one embodiment, the
reporting of the alpha-derived neuromarker value comprises a visual
reporting wherein a target, representing in real-time the
alpha-derived neuromarker value of the subject, is displayed. Said
target, representing the alpha-derived neuromarker value, may move
along one or more directions on a display screen. The normalization
of the alpha-derived neuromarker allows an easy representation of
the alpha-derived neuromarker, since the values' scale of the
alpha-derived neuromarker is fixed and independent from the
subject.
According to an alternative embodiment, the alpha-derived
neuromarker value is represented in relation to a reference state.
According to this embodiment, the target representing the subject
alpha-derived neuromarker value may move toward or away from a
location corresponding to a representation of said reference state.
The reference state may be defined as the alpha-derived neuromarker
value obtained by the subject at the beginning of each training
session or the alpha-derived neuromarker value obtained when the
subject is doing a certain task, such as, but not limited to,
reading, speaking, listening etc. Alternatively, the reference
state may be defined by the alpha-derived neuromarker value obtain
by the subject before the beginning of the self-paced
neuromodulation training (i.e. before the first training session).
The reference state may be further defined as an average
alpha-derived neuromarker value obtained from a representative
population not including the subject undergoing the self-paced
neuromodulation training.
According to the embodiment wherein the alpha-derived neuromarker
value is reported using visual means, an object on the screen,
which position, size, color, or any other parameters can be
modulated by said alpha-derived neuromarker value, is reported to
the subject. For instance, it can be the representation of a plane
or a hot-air balloon, whose altitude is modulated by the
alpha-derived neuromarker value, as shown in FIG. 2. Said visual
means may alternatively be a lights source such as but not limited
to LEDs or LASERs device.
According to the embodiment wherein the alpha-derived neuromarker
value is reported using auditory means, a sound, the amplitude of
which is directly modulated by said alpha-derived neuromarker
value, is reported to the subject. The sound can be a simple beep,
water flowing, waves, rain, dongs, any kind of music, or any other
sound which can be modulated in amplitude or frequency.
According to one embodiment, the improvement of the alpha-derived
neuromarker value for the subject is realized through a learning
process.
According to one embodiment, the learning process can be
implemented according to the principles of operand conditioning.
The generation of the targeted cerebral activity, improving alpha
phase concentration or alpha phase synchrony can be rewarded by a
positive stimulus (positive reinforcement) such as, by means of
non-limiting example, diffusion of pleasant music, showing of nice
images and/or an interesting video.
According to one embodiment, a deterioration of the alpha-derived
neuromarker, obtained from the subject, is associated with the
removal of the pleasant stimulus (negative reinforcement). Said
alpha-derived neuromarker deterioration can also be associated with
the communication of negative stimuli (positive punishment) such
as, by means of non-limiting example, diffusion of unpleasant
music, interruption of a pleasant music and/or interruption of an
interesting video. According to one embodiment, the improvement of
the alpha-derived neuromarker value back to a better state is
rewarded by the removal of an unpleasant negative stimulation
(negative punishment) and further positive reinforcement.
According to one embodiment, the learning process is implemented
according to the principles of self-control by giving the subject a
continuous real time representation of the alpha-derived
neuromarker in order to allow said subject to gain control and
modify the alpha-derived neuromarker through the desired state.
According to one embodiment, the learning process can be
implemented with any other learning strategy or combination of
them.
According to one embodiment, the system for biofeedback training
described in patent publication EP 3 181 043 is used to promote
subject learning by providing a reward to the subject; said reward
being based on the difference between the alpha-derived neuromarker
and a computed threshold calculated according to the
computer-implemented method of said patent publication.
According to one embodiment, the self-paced neuromodulation methods
of the present invention are a long-term cure for the subject.
According to one embodiment, the self-paced neuromodulation methods
are controlled by a subject.
According to one embodiment, the self-paced neuromodulation methods
are supervised by a skilled physician. The skilled physician may
train, especially during the first session, the subject to the
utilization of the methods for self-paced neuromodulation.
According to one embodiment, the self-paced neuromodulation methods
are used by the subject alone. In this embodiment, the subject may
use the self-paced neuromodulation methods at his residence.
In the view of the above detailed description, one skilled in the
art could implement the method according to the present invention.
Especially, the implementation of the method may use the following
tools: an open source toolbox for Brain-Computer Interface research
such as that available on https://sccn.ucsd.edu/wiki/BCILAB; a
software platform dedicated to designing, testing and using
brain-computer interfaces such as that available on
http://openvibe.inria.fr/. OpenViBE platform is a software for
brain-computer interface and real time neurosciences. It provides
components for digital signal processing and visualization of EEG
signal. It can be extended with modules in C++, Matlab and Python.
a software suite for EEG data acquisition, stimulus presentation,
and brain monitoring applications such as that available on
http://www.schalklab.org/research/bci2000;
While various embodiments have been described and illustrated, the
detailed description is not to be construed as being limited
hereto. Various modifications can be made to the embodiments by
those skilled in the art without departing from the true spirit and
scope of the disclosure as defined by the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a schematic block diagram of the self-paced
neuromodulation methods in which the present invention may be
embodied.
FIG. 2 is an example of alpha-derived neuromarker value reported
using visual means.
FIG. 3 is a box-plot showing the evolution through sessions of the
alpha phase synchrony neuromarker when electroencephalographic
signals are acquired with eyes open (EO), eyes closed (EC) or
averaged across all blocks during self-paced neuromodulation
training session. Training session number is represented on the
x-axis and the normalized alpha phase synchrony neuromarker value
is represented on the y-axis. The black line shows the positive
trend of the alpha phase synchrony neuromarker over the training
sessions.
FIG. 4 is a box-plot showing intra-session alpha phase synchrony
evolution averaged across all sessions when electroencephalographic
signals are acquired with eyes open (EO), eyes closed (EC) or
during self-paced neuromodulation training. Block number is
represented on the x-axis and the normalized alpha phase synchrony
value is represented on the y-axis. The line shows the positive
trend over blocks.
FIG. 5 is a bar plot showing the progression of clinical scores
(Dallas scale, self-reported Body Pain (EVA), Anxiety and
Depression scale (HAD) and Hamilton scores) averaged for the 16
patients, recorded before the self-paced neuromodulation training
(gray) and after (black).
EXAMPLES
The present invention is further illustrated by the following
examples.
Example 1--Validation of the System and Method to Reinforce
Self-Modulation of Pain Pathways in a Subject
The system and method for self-modulation of pain pathways proposed
in the detailed description has been validated on real data.
EEG data were acquired on-line and the stimulation representing the
alpha synchrony neuromarker value was communicated in real-time to
the subject. The present method will be considered successful if an
improvement of clinical score parameters will be observed over time
from the subject.
Materials and Methods
Recordings
The electroencephalography (EEG) data was collected using a
19-channels smartBCI EEG system (Saint-Petersburg, Russia) with 19
silver-chloride electrodes fitted to a neoprene cap.
The 19 electrodes were approximately located at the extended 10-20
locations Fp1, Fp2, F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3,
Pz, P4, T6, O1, and O2, while referenced to linked ear lobes A1 and
A2. Each electrode was connected to the subject's scalp by the mean
of electrolyte gel using a syringe with blunt needle. The headset
was connected wirelessly to the participant laptop and interfaced
with the Mensia NeuroRT Training.
Data are acquired during 20 training sessions each composed of 6
blocks of 5 minutes, preceded by recording of 2 minutes wherein the
subject keeps the eyes-open (EO) and recording of 2 minutes wherein
the subject keeps the eyes-closed (EC).
Population
Patients were enrolled at a tertiary day-care clinic for physical
medicine and rehabilitation after giving their informed consent
about the research. Inclusion criteria comprised the presence of
chronic back pain resistant any form of standard therapeutic
approach including a week-long intensive multidisciplinary approach
made of drug, physiotherapy, psychotherapy. The control population
was recruited from participants who responded positively to the
one-week intensive treatment. In order to limit heterogeneity, only
female participants were included in the study. Patients were told
they could leave the research protocol at any time and without
condition.
In total, 16 patients and 10 control subjects were included in the
study.
Data Processing
For each block of each session: raw signal was band-pass filtered
using a 1-45 Hz 1st-order Butterworth filter, and band-stop
filtered in the frequency range 47-53 Hz with a 3rd-order
Butterworth notch filter to suppress 50 Hz power line interference,
filtered signal was further processed to remove signal epochs
comprising ocular artefacts using a mean covariance matrix, and
alpha phase synchrony neuromarker was computed across time.
Electroencephalographic signal was processed as described on-line
to show to the subject a figurative representation of the alpha
phase synchrony neuromarker.
In order to study the progression of the alpha phase synchrony
neuromarkers across time, all subjects' recordings collected were
as well stored to be processed off-line as described above. For the
statistical analysis, the slopes of neuromarkers progression over
training sessions and training blocks are computed for all patients
with a Pearson correlation, proving a correlation coefficient R and
a p-value.
Clinical Scales
In order to assess the clinical progression of the subjects,
several health questionnaires were proposed to the subject before
and after the neurofeedback sessions. The health questionnaires
including: A self-reported Body Pain visual analogous scale (EVA),
from zero (no pain) to ten (maximal pain one can imagine); The
Hospital Anxiety and Depression scale (HAD) ("The hospital anxiety
and depression scale", Acta psychiatrica scandinavica, Zigmond, A.
S. and Snaith R. P., 1983), an international self-reported scale
used to assess depress or anxiety state from zero (normal) to
twenty-one points for each marker; each subscale is considered
clinically significant over eleven and the maximal cumulated score
is forty-two; the HAD is used for its sensitivity to variations of
mental state; The DALLAS scale ("The Development of the Dallas Pain
Questionnaire: An Assessment of the Impact of Spinal Pain on
Behavior" Spine, Lawlis et al., 1989) is a self-reported quality of
life scale for patients with low back pain assessing the impact on
everyday quality of life: work and leisure, anxiety, depression,
and sociability; each subpart varies from zero to one hundred
percent. The HAMILTON anxiety rating scale ("The assessment of
anxiety states by rating", British journal of medical psychology,
Hamilton, 1959) includes fourteen items (quality of sleep, muscular
tension, fears, somatic symptoms in cardio-vascular and respiratory
systems, neuro-vegetative, etc.) each scoring from zero to four,
summing up to a maximum value of fifty-six, which is considered
clinically significant above twenty; this scale is particularly
useful for our patients who are suffering from multiple pain and
specifically muscle pain; it also proves relevant to capture
variation.
For the evolution of these clinical scores between before and after
neurofeedback, a Wilcoxon signed-rank test is applied for each
score on paired values.
Results
FIG. 3 shows the alpha phase synchrony neuromarker evolution
between session for EEG signal acquired for the subject with eyes
open (EO), eyes closed (EC) and during the self-paced
neuromodulation training averaged across all blocks of a session.
Data acquired with eyes closed shows an elevated alpha activity as
compared to the ones acquired with open eyes. Furthermore, the
alpha phase synchrony neuromarker level before training shows an
elevation over the eyes open recording, which possibly captures the
brain activity related to the mental task proposed by the
neuromodulation training. Finally, the recordings of the alpha
phase synchrony neuromarker during training present a significant
positive trend (p=0.0017) and a positive Pearson product-moment
correlation coefficient (Pearson corr.=0.63).
FIG. 4 shows the interquartile evolution of the alpha phase
synchrony neuromarker at rest (block 1, EEG signal acquired for the
subject with eyes open EO and eyes closed EC self-paced
neuromodulation before training) and during the self-paced
neuromodulation training over consecutive blocks. It shows that EC
recordings have an elevated alpha phase synchrony neuromarker
value, which was expected due to resynchronization of visual
cortex. Similarly, the recordings of the alpha phase synchrony
neuromarker from block 1 to 6 present a significant positive trend
(p=0.0021) and a positive Pearson product-moment correlation
coefficient (Pearson corr.=0.63). This improvement over the blocks
reflects changes in brain activity induced by the fact that the
subject is doing the self-paced neuromodulation training task.
Changes in neurophysiological activity are only meaningful once
associated with observed changes in symptoms. FIG. 5 shows the
progression for Dallas scale, self-reported Body Pain (EVA),
Anxiety and Depression scale (HAD) and Hamilton scores for the 16
patients included in the study. Median and median absolute
deviation are plotted before and after the neurofeedback sessions.
Clinical scores show reduction between before and after the
self-paced neuromodulation training, reflecting the impact of the
training.
Conclusions
This pilot study validates the self-paced neuromodulation approach
proposed in the present invention. According to the results, the
use of alpha phase synchrony neuromarker for self-paced
neuromodulation allows an effective modification of the
neurophysiological activity of the subject under training. Indeed,
the alpha phase synchrony neuromarker efficiently marks brain
activity patterns associated to pain pathways, therefore allowing
the reinforcement of self-modulation of pain pathways in a
subject.
* * * * *
References